Date

Author

Share

Metadata

Abstract

Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have
suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to
confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk,
we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268).
Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r2.0.8]) and PA were
invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a
dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were
categorized as inactive. Interaction analyses were performed within each study by including the FTO6PA interaction term in
an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction
terms. In adults, the minor (A2) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20–1.26), but
PA attenuated this effect (pinteraction = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity
less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19–1.25) than in the inactive group (odds ratio = 1.30/
allele, 95% CI 1.24–1.36). No such interaction was found in children and adolescents.
Conclusions: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults,
highlighting the importance of PA in particular in those genetically predisposed to obesity.

Description

There are 116 authors. Only a few of them have been given author entries.